TY - JOUR
T1 - Elastomeric free-form blood vessels for interconnecting organs on chip systems
AU - Zhang, Weijia
AU - Zhang, Yu Shrike
AU - Bakht, Syeda Mahwish
AU - Aleman, Julio
AU - Shin, Su Ryon
AU - Yue, Kan
AU - Sica, Marco
AU - Ribas, João
AU - Duchamp, Margaux
AU - Ju, Jie
AU - Sadeghian, Ramin Banan
AU - Kim, Duckjin
AU - Dokmeci, Mehmet Remzi
AU - Atala, Anthony
AU - Khademhosseini, Ali
N1 - Funding Information:
The authors gratefully acknowledge funding from the Defense Threat Reduction Agency (DTRA) under Space and Naval Warfare Systems Center Pacific (SSC PACIFIC) Contract No. N6601-13-C-2027. The authors also acknowledge funding from the Office of Naval Research Young National Investigator Award, the National Institutes of Health (EB012597, AR057837, DE021468, HL099073, R56AI105024), and the Presidential Early Career Award for Scientists and Engineers (PECASE). W. Z. acknowledges funding from China's 1000 Young Talents Program, Shanghai Young Eastern Scholar, Shanghai Pujiang Program (14PJ1404300), and NSFC (31501555). J. R. acknowledges the support from the Portuguese Foundation for Science and Technology (FCT; SFRH/BD/51679/2011). The publication of this material does not constitute approval by the government of the findings or conclusions herein.
Publisher Copyright:
© The Royal Society of Chemistry 2016.
PY - 2016
Y1 - 2016
N2 - Conventional blood vessel-on-a-chip models are typically based on microchannel-like structures enclosed within bulk elastomers such as polydimethylsiloxane (PDMS). However, these bulk vascular models largely function as individual platforms and exhibit limited flexibility particularly when used in conjunction with other organ modules. Oftentimes, lengthy connectors and/or tubes are still needed to interface multiple chips, resulting in a large waste volume counterintuitive to the miniaturized nature of organs-on-chips. In this work, we report the development of a novel form of a vascular module based on PDMS hollow tubes, which closely emulates the morphology and properties of human blood vessels to integrate multiple organs-on-chips. Specifically, we present two templating strategies to fabricate hollow PDMS tubes with adjustable diameters and wall thicknesses, where metal rods or airflow were employed as the inner templates, while plastic tubes were used as the outer template. The PDMS tubes could then be functionalized by human umbilical vein endothelial cells (HUVECs) in their interior surfaces to further construct elastomeric biomimetic blood vessels. The endothelium developed biofunctionality as demonstrated by the expression of an endothelial biomarker (CD31) as well as dose-dependent responses in the secretion of von Willebrand factor and nitric oxide upon treatment with pharmaceutical compounds. We believe that with their clear advantages including high optical transparency, gas permeability, and tunable elasticity matching those of native blood vessels, these free-form PDMS vascular modules can supplement bulk vascular organoids and likely replace inert plastic tubes in integrating multiple organoids into a single microfluidic circuitry.
AB - Conventional blood vessel-on-a-chip models are typically based on microchannel-like structures enclosed within bulk elastomers such as polydimethylsiloxane (PDMS). However, these bulk vascular models largely function as individual platforms and exhibit limited flexibility particularly when used in conjunction with other organ modules. Oftentimes, lengthy connectors and/or tubes are still needed to interface multiple chips, resulting in a large waste volume counterintuitive to the miniaturized nature of organs-on-chips. In this work, we report the development of a novel form of a vascular module based on PDMS hollow tubes, which closely emulates the morphology and properties of human blood vessels to integrate multiple organs-on-chips. Specifically, we present two templating strategies to fabricate hollow PDMS tubes with adjustable diameters and wall thicknesses, where metal rods or airflow were employed as the inner templates, while plastic tubes were used as the outer template. The PDMS tubes could then be functionalized by human umbilical vein endothelial cells (HUVECs) in their interior surfaces to further construct elastomeric biomimetic blood vessels. The endothelium developed biofunctionality as demonstrated by the expression of an endothelial biomarker (CD31) as well as dose-dependent responses in the secretion of von Willebrand factor and nitric oxide upon treatment with pharmaceutical compounds. We believe that with their clear advantages including high optical transparency, gas permeability, and tunable elasticity matching those of native blood vessels, these free-form PDMS vascular modules can supplement bulk vascular organoids and likely replace inert plastic tubes in integrating multiple organoids into a single microfluidic circuitry.
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U2 - 10.1039/c6lc00001k
DO - 10.1039/c6lc00001k
M3 - Article
AN - SCOPUS:84966350657
VL - 16
SP - 1579
EP - 1586
JO - Lab on a Chip - Miniaturisation for Chemistry and Biology
JF - Lab on a Chip - Miniaturisation for Chemistry and Biology
SN - 1473-0197
IS - 9
ER -